Background & Aims With a deeper understanding of the anatomy of the ampulla of Vater, the technique of duodenum-preserving pancreatic head resection (DPPHR) has emerged. Alongside advancements in minimally invasive laparoscopic techniques, single-incision laparoscopic surgery (SILS) and laparoscopic DPPHR have been developed. However, due to the inherent complexity of the procedure, combining "single-incision" with "preservation of the duodenal pancreatic head" has remained challenging. Therefore, our team sought to simplify and improve this approach by attempting single-incision laparoscopic DPPHR (SILDPPHR) with the addition of a 12 mm Trocar at the left rib margin, referred to as SILDPPHR+1. This study was primarily conducted to evaluate the feasibility and effectiveness of SILDPPHR+1 with fluorescence-guided navigation.Methods The clinical data of 8 patients who underwent SILDPPHR+1 with fluorescence-guided navigation in the Department of Hepatobiliary and Pancreatic Surgery of Sichuan Provincial People's Hospital between February 2022 and May 2023 were retrospectively analyzed. SILDPPHR+1 involved the integration and refinement of techniques, including traditional 5-port laparoscopic DPPHR, single-incision laparoscopic surgery, and indocyanine green cholangiography; techniques such as suture suspension and cross traction were applied to achieve optimal exposure within limited operating space; emphasizing the protection of the pancreaticoduodenal artery arch, bile duct-pancreatic segment, and the duodenum, along with the use of pancreaticojejunostomy techniques to reduce postoperative complications.Results All 8 patients who underwent fluorescence-guided SILDPPHR+1 completed the surgery successfully, with no intraoperative conversions to 5-port laparoscopic or open procedures. The average surgical duration was (360±68) min, and intraoperative blood loss was (84±26) mL, with no intraoperative transfusions required. Pathological examination revealed 5 cases of intraductal papillary mucinous neoplasm of the pancreas, 1 case of mucinous cystic neoplasm, and 2 cases of chronic pancreatitis. All 8 cases achieved radical resection, with no severe gastrointestinal dysfunction after operation. Oral intake was resumed after an average of 5 d, and the average length of hospital stay was (9±2) d. During a follow-up period of (7.8±4.6) months, none of the 8 patients experienced tumor recurrence or gastrointestinal dysfunction. There were no bile leaks or duodenal ischemic necrosis, but 2 cases developed grade A pancreatic fistula, and 1 case had biliary stricture.Conclusion In appropriately selected cases and within experienced hepatobiliary and pancreatic surgery centers, performing fluorescence-guided navigation SILDPPHR+1 is safe and feasible.